As described previously, an experimental intravenous immune globulin, HCIGIV, which was derived from about 200 anti-HCV positive plasma units and had high-levels of antibodies to HCV envelope glycoproteins, E1 and E2, was able to neutralize a low-titer HCV inoculum, 64 CID50/mL. In contrast, a commercial IGIV prepared from anti-HCV EIA-2 screened units was unable to do so. An Albumin solution was also used as a control to demonstrate the viability of the low-titer inoculum. Chimpanzees were used to detect residual infectivity if the inoculum was not neutralized. When the protected chimpanzee was subsequently challenged with the same low-titer inoculum for checking its susceptibility to HCV, anti-HCV EIA-3 was unexpectedly found positive within one week. We detected the unique immune responses in the challenged chimpanzee, such as detection of both anti-hypervariable region 1 (HVR1) of the E2 region and the anti-HCV core region. Anti-HVR1 was detected within one week post challenge in the protected chimpanzee but was not detected in any of the two infected chimpanzees. Anti-nonstructural region 4 (anti-NS4) occurred within one week post challenge but its elevation was transient and biphasic, not monophasic as in the other two infected animals. The temporal profile for anti-nonstructural region 3 (anti-NS3) was, however, similar in all three infected chimpanzees. Thus, immune priming seems to have occurred before infectious challenge of the protected chimpanzee. We can conclude, however, that neutralizing antibodies can be present in anti- HCV positive plasma and HCIGIV would have therapeutic utility. We assessed the levels of anti-B19, protective IgG antibodies to parvovirus B19, in immune globulin (Ig) products. This is to evaluate whether the levels of anti-B19 would be varied among Ig products. In addition, because of the recently implemented B19 mini-pool screening by some fractionators as an in-process test to lower the viral load of manufacturing pools and thus to reduce or eliminate B19 in plasma derivatives, we want to evaluate whether such screening would reduce the anti-B19 levels in products. Initially, two EIA kits were used; one investigative kit is coated with denatured, recombinant capsid protein VP1while the other PMA-licensed kit is coated with undenatured, recombinant capsid protein VP2. VP1 contains VP2 sequence at its C- terminus. An international standard, 100 IU/mL of anti-B19 IgG, was used to set up a respective semi-quantitative assay to measure anti-B19 IgG levels. However, two assays were not equal. Anti-B19 levels were very much lower when using the kit coated with denatured VP1 as an antigen. Other publications as well as our results appeared to indicate the necessity of using undenatured parvovirus B19 antigen to accurately detect parvovirus B19 IgG levels. Hence, the anti-VP2 kit was solely used for evaluating the Ig products. Preliminary results indicated that anti-B19 levels varied among Ig products. The intravenous immune globulin (IGIV) lots made by one manufacturer had significantly lower levels of anti-B19. More thorough study is needed before final conclusion can be made. Recently several IGIV lots made by one manufacturer did not meet the potency specification for anti-measles antibodies. In collaboration with scientists in OVRR, we measured the levels of anti-measles antibodies in IGIV lots made by several manufacturers by a neutralizing antibody assay. Preliminary results indicate that the levels of anti-measles antibodies varied depending upon the manufacturing procedures employed by IGIV manufacturers. Study is still in progress.